Elevated expression of a pharmacologic Polycomb signature predicts poor prognosis in gastric and breast cancer

Abstract

Aim: Polycomb Group complexes are epigenetic repressors that silence tumor suppressive genes. Studies demonstrated that pharmacologic inhibition of Polycomb Group complexes with 3-deazaneplanocin A (DZNeP) induces cancer cell death by re-expressing silenced genes. Here we evaluate the prognostic significance of DZNeP target genes in gastric and breast cancer. Patients & methods/materials: The prognostic impact of a DZNeP-regulated gene signature was investigated using the KM Plotter and cBio Portal resources containing microarray data from tumor tissue. Results: We report that elevated expression of DZNeP targets is associated with poor clinical outcome in gastric and breast cancer. In gastric cancer, elevated expression of DZNeP signature is inversely correlated with decreased overall survival. In breast cancer, DZNeP signature predicted poor prognosis in HER2+ tumors but not in HER2^- neoplasms. Conclusion: These findings demonstrate that DZNeP target genes are not predictive of better but rather of poor clinical outcome in gastric and breast cancer.

Keywords::

• cancer
• DZNeP
• epigenetics
• EZH2
• Polycomb
• prognostic
• signature

Availability of data & material

The datasets generated during and/or analyzed during the current study are all publicly available in the KM Plotter resource (http://kmplot.com/analysis/) and the cBio Portal (www.cbioportal.org/).

Acknowledgements

The authors thank the developers of ‘‘Kaplan–Meier Plotter’ and the ‘‘cBio Portal’ for creating these useful platforms.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/full/10.2217/epi-2017-0074